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Biomedical subjects

L W Stevenson

Publications and source records attributed to L W Stevenson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Excessive oxygen deficit during low-level exercise in heart failure.

Although peak oxygen consumption is reduced in patients with symptomatic heart failure, the degree of limitation during routine activity often appears greater or lesser than expected from peak capacity. This study was undertaken to determine whether abnormalities could be detected during the initiation of steady-state low-level exercise, approximating routine activity, which were distinct from limitation in peak capacity. We sought to determine whether a delay in the integrated response to the increased metabolic demand caused by exercise, assessed by the oxygen deficit incurred between exercise initiation and the achievement of steady-state oxygen uptake, was present in heart failure. Low-level and symptom-limited maximal exercise tests in 33 ambulatory patients with heart failure were analyzed and compared with 9 tests in control subjects. Oxygen deficit was determined during the 8-minute low-level exercise at 20 W. During maximal exercise, as expected, patients with heart failure had lower peak oxygen uptake (16 +/- 4 vs 31 +/- 6 ml/kg/min) and anaerobic threshold (870 +/- 270 vs 1,180 +/- 370 ml/min) than controls. After 8 minutes of low-level exercise, the oxygen deficit was higher in patients than in controls (550 +/- 230 vs 270 +/- 100 ml, respectively, p < 0.01). Among patients with heart failure, the oxygen deficit did not correlate with peak oxygen uptake or anaerobic threshold. Although the time to steady-state heart rate was later in patients with heart failure, this delay did not correlate with oxygen deficit. The oxygen deficit represents a distinct abnormality of exercise response that may reflect impaired central and peripheral responses to the initiation of exercise.

Adult↗
PubMed1995

Amiodarone and torsades de pointes in patients with advanced heart failure.

Amiodarone is considered to be safe in patients with prior QT prolongation and torsades de pointes taking class I antiarrhythmic agents who require continued antiarrhythmic drug therapy. However, the safety of amiodarone in advanced heart failure patients with a history of drug-induced torsades de pointes, who may be more susceptible to proarrhythmia, is unknown. Therefore, the objective of this study was to assess amiodarone safety and efficacy in heart failure patients with prior antiarrhythmic drug-induced torsades de pointes. We determined the history of torsades de pointes in 205 patients with heart failure treated with amiodarone, and compared the risk of sudden death in patients with and without such a history. To evaluate the possibility that all patients with a history of torsades de pointes would be at high risk for sudden death regardless of amiodarone treatment, we compared this risk in patients with a history of torsades de pointes who were and were not subsequently treated with amiodarone. Of 205 patients with advanced heart failure, 8 (4%) treated with amiodarone had prior drug-induced torsades de pointes. Despite similar severity of heart failure, the 1-year actuarial sudden death risk was markedly increased in amiodarone patients with than without prior torsades de pointes (55% vs 15%, p = 0.0001). Similarly, the incidence of 1-year sudden death was markedly increased in patients with prior torsades de pointes taking amiodarone compared with such patients who were not subsequently treated with amiodarone (55% vs 0%, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Risk of arterial embolization in 224 patients awaiting cardiac transplantation.

Of patients awaiting cardiac transplantation, 10% to 20% die before a donor heart becomes available. Embolization of left ventricular thrombus is a source of morbidity and mortality in this population. To define the incidence and possible risk factors for systemic arterial embolization, we examined the frequency of arterial embolic events and their relation to clinical, hemodynamic, and echocardiographic variables in 224 consecutive outpatients awaiting cardiac transplantation (left ventricular ejection fraction 0.20 +/- 0.07 and left ventricular end-diastolic dimension 76 +/- 11 mm). Over a follow-up period of 301 +/- 371 days, during which 82 (37%) patients received warfarin, arterial embolization occurred in 6 (3%) patients, 1 of whom was receiving and 5 of whom were not receiving warfarin (difference not specifically significant). The risk of embolization was not statistically different in patients with atrial fibrillation, previous embolization, or left ventricular thrombus on transthoracic echocardiogram, regardless of warfarin therapy. Cumulative risk of sudden death was similar for patients with or without echocardiographically documented left ventricular thrombus. Nonfatal bleeding complications associated with warfarin therapy occurred in 2 (2%) patients. Thus in patients who are awaiting cardiac transplantation and who receive anticoagulation therapy for left ventricular thrombus, atrial fibrillation, or previous arterial embolization, the incidence of clinically detectable arterial embolization is low despite severe ventricular dilatation. Embolization is not likely a major cause of sudden death or morbidity in this population.

Cardiomyopathy, Dilated↗
PubMed1995

Improvement in exercise capacity of candidates awaiting heart transplantation.

OBJECTIVES: This study determined the frequency of improvement in peak oxygen uptake and its role in reevaluation of candidates awaiting heart transplantation. BACKGROUND: Ambulatory candidates for transplantation usually wait > 6 months to undergo the procedure, and during this period symptoms may lessen, and peak oxygen uptake may improve. Whereas initial transplant candidacy is based increasingly on objective criteria, there are no established guidelines for reevaluation to determine who can leave the active waiting list. METHODS: All ambulatory transplant candidates with initial peak oxygen uptake < 14 ml/kg per min were identified. Of 107 such patients listed, 68 survived without early deterioration or transplantation to undergo repeat exercise. A strategy of reevaluation using specific clinical criteria and exercise performance was tested to determine whether patients with improved oxygen uptake could safely be followed without transplantation. RESULTS: In 38 of the 68 patients, peak oxygen uptake increased by > or = 2 ml/kg per min to a level > or = 12 ml/kg per min after 6 +/- 5 months, together with an increase in anaerobic threshold, peak oxygen pulse and exercise heart rate reserve and a decrease in heart rate at rest. Increased peak oxygen uptake was accompanied by stable clinical status without congestion in 31 of 38 patients, and these 31 were taken off the active waiting list. At 2 years, their actuarial survival rate was 100%, and the survival rate without relisting for transplantation was 85%. CONCLUSION: Reevaluation of exercise capacity and clinical status allowed removal of 31 (29%) of 107 ambulatory transplant candidates from the waiting list with excellent early survival despite low peak oxygen uptake on initial testing. The ability to increase peak oxygen uptake, particularly with increased peak oxygen pulse, may indicate improved prognosis as well as functional capacity and, in combination with stable clinical status, may be an indication to defer transplantation in favor of more compromised candidates.

Adolescent↗
PubMed1994

Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction.

Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction have a high but variable annual mortality and some may benefit from myocardial revascularization. This study aimed to evaluate the prognostic value of positron emission tomography (PET), and its interrelation with the choice of medical therapy or revascularization for predicting survival and improvement in symptoms of heart failure in patients with CAD and LV dysfunction. Ninety-three consecutive patients with angiographic CAD and a mean LV ejection fraction of 0.25 who underwent cardiac PET studies for assessment of hypoperfused yet viable myocardium ("mismatch pattern") using N-13 ammonia and 18-F deoxyglucose were followed up for an average of 13.6 months. Fifty patients underwent medical treatment and 43 underwent revascularization. The Cox model analysis showed that the extent of mismatch had a negative effect (p = 0.02), whereas revascularization had a positive effect on survival (p = 0.04). The annual survival probability of patients with mismatch receiving medical therapy was lower than of those without mismatch (50 vs 92%, p = 0.007). Patients with mismatch who underwent revascularization had a higher survival rate than those treated medically (88 vs 50%, P = 0.03). The presence of mismatch also predicted improvement in heart failure symptoms after revascularization (p < 0.001). These results suggest that the presence of mismatch in patients with CAD and severe LV dysfunction is associated with poor annual survival with medical therapy. Revascularization in patients with PET mismatch appears to be associated with improved survival and heart failure symptoms.

Aged↗
PubMed1994

Prediction of improvement in recent onset cardiomyopathy after referral for heart transplantation.

OBJECTIVES: The purpose of this investigation was to determine how often left ventricular function improves in recent onset dilated cardiomyopathy of sufficient severity to cause referral for heart transplantation and how to predict this improvement at the time of evaluation for transplantation. BACKGROUND: Improvement has been reported to occur frequently in patients with acute dilated cardiomyopathy but has not been described specifically in these patients referred for transplantation. To avoid potentially needless transplantation, it would be useful to know the frequency of improvement and how to predict it in these patients. METHODS: A consecutive series of 297 patients with primary dilated cardiomyopathy evaluated for heart transplantation was reviewed to identify those with onset of heart failure symptoms within the preceding 6 months and to examine their outcome. The clinical, echocardiographic, hemodynamic and laboratory profiles of patients with improvement in left ventricular function (defined as an increase in left ventricular ejection fraction > or = 0.15 to a final ejection fraction of > or = 0.30) were compared with those of patients without improvement to assess which variables might predict improvement. RESULTS: Of 49 patients with recent onset dilated cardiomyopathy, 13 (27%) showed improvement, with an increase in mean left ventricular ejection fraction from 0.22 +/- 0.08 to 0.49 +/- 0.09. All patients with improvement had survived without heart transplantation at 43 +/- 29 months. Survival time was shorter in the remaining 36 patients without improvement with recent onset cardiomyopathy than in the 248 with chronic symptoms (p = 0.03) and in younger compared with older patients with recent onset cardiomyopathy (p = 0.0001). By multivariate analysis, predictors of improvement were shorter duration of symptoms, lower pulmonary wedge and right atrial pressures and higher serum sodium levels. CONCLUSIONS: A minority of patients with dilated cardiomyopathy and symptoms for < or = 6 months will have marked improvement in left ventricular function, after which prognosis is excellent despite previous referral for heart transplantation. Those with symptom duration > 3 months and more severe initial decompensation as reflected by higher filling pressures and lower serum sodium levels are unlikely to show improvement and may require earlier consideration for heart transplantation.

Actuarial Analysis↗
PubMed1994

Timing of sudden death in patients with heart failure.

OBJECTIVES: The purpose of this study was to determine the timing of sudden death in patients with advanced heart failure. BACKGROUND: The frequency of sudden cardiac death and myocardial infarction is greatest in the morning hours, suggesting that physiologic processes associated with morning activities may trigger these events. In patients with advanced heart failure, a variety of mechanisms may cause sudden death, and the frequency of their occurrence may differ from that in other patient groups, perhaps altering the timing of sudden death in heart failure. METHODS: Deaths among 566 consecutive patients followed up after treatment for advanced heart failure were prospectively categorized as sudden death, death due to heart failure or noncardiac death. For 72 sudden deaths the time of death was determined from witnesses to the event and from death certificates. RESULTS: Sudden death occurred 2.5 times more frequently between 6:01 AM and 12 noon than in the three other 6-h intervals, with 46% of deaths occurring during this period (p < 0.005). The morning peak occurred both in patients with coronary artery disease and in those with nonischemic causes of heart failure. CONCLUSIONS: Despite a variety of potential mechanisms of sudden death and underlying causes of heart disease in patients with heart failure, the 24-h distribution of sudden death in these patients is similar to that observed in other patient groups. Morning surges in sympathetic nervous system activity may promote a variety of sudden death mechanisms, including ischemic and nonischemic arrhythmias.

Adult↗
PubMed1994

Selection and management of patients for cardiac transplantation.

The limited availability of donor hearts for cardiac transplantation has focused interest on the provision of alternative therapies and on the establishment of more objective criteria for determining which candidates will benefit. Indications now emphasize exercise capacity and reevaluation on optimal medical therapy rather than ejection fraction or previous history. Pharmacologic and mechanical bridges to transplantation are increasingly used for the growing population of hospitalized candidates. Preserving the option of outpatient transplantation prior to deterioration will require better assessment of sudden death risk and hemodynamic risk. Patients with advanced heart failure form a unique population, rarely represented in large trials, for whom prognosis and therapy continue to improve.

Cardiotonic Agents↗
PubMed1994

The impending crisis awaiting cardiac transplantation. Modeling a solution based on selection.

BACKGROUND: Each month, the number of transplant candidates added to the waiting list exceeds the number of transplantations performed, and many outpatients deteriorate to require transplantation urgently. The current list of 2400 candidates and the average wait of 8 months continue to increase. METHODS AND RESULTS: To determine the size at which the outpatient and critical candidate pools will stabilize, population models were constructed using current statistics for donor hearts, candidate listing, sudden death, and outpatient decline to urgent status and revised to predict the impact of alterations in policies of candidate listing. If current practices continue, within 48 months the predicted list will stabilize as the sum of an estimated 270 hospitalized candidates, among whom, together with newly listed urgent candidates, all hearts will be distributed and 3700 outpatient candidates with virtually no chance of transplantation unless they deteriorate to an urgent status. Decreasing the upper age limit now to 55 years would reduce the number listed each month by 30% and result within 48 months in a list of only 1490. The list could also be decreased by 30%, however, if it were possible to list only a candidate group with an 80% chance (compared with 52% estimated currently) of sudden death or deterioration during the next year. With this strategy, the waiting list would equilibrate within 48 months to one-third the current size, with 50% of hearts for outpatient candidates, who would then have an 11% chance each month of receiving a heart compared with 0% if recent policies prevail. Total deaths, with and without transplantation, would be minimized by this rigorous selection of outpatient candidates. CONCLUSIONS: This study implies that immediate provisions should be made to limit candidate listing and revise expectations to reflect the diminishing likelihood of transplantation for outpatient candidates. Future emphasis should be on improved selection of candidates at highest risk without transplantation.

Computer Simulation↗
PubMed1994

Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection.

BACKGROUND: The relative intracoronary flow reserve has been found to be reduced during acute transplant rejection, but the effects of rejection on absolute flows at rest and during hyperemia have not been established previously. This has now become possible through noninvasive quantification of myocardial blood flow with positron emission tomography. METHODS AND RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia was quantified in 10 transplant patients (group A) during an acute, biopsy-proven rejection episode and again after successful immunosuppressive treatment and in 6 transplant patients (group B) without prior rejection episode. In group A patients, MBF during rejection averaged 1.7 +/- 0.3 mL.min-1.g-1 at rest and 2.5 +/- 0.9 mL.min-1.g-1 during hyperemia; after recovery, MBF at rest had declined to 1.2 +/- 0.3 mL.-1.g-1 (P < .001) but had increased to 3.9 +/- 1.1 mL.-1.g-1 (P < .001) during hyperemia. Flows after recovery from rejection were similar to those in the group B patients (0.9 +/- 0.2 and 3.9 +/- 0.7 mL.min-1.g-1). Flow reserve in the group A patients was only 1.5 +/- 0.5 during rejection but improved to 3.4 +/- 0.9 at recovery (P < .001) and thus remained lower than in the control patients (4.5 +/- 0.7, P < .05). Minimal coronary resistance during dipyridamole vasodilation was elevated during rejection (40 +/- 11 mm Hg.mL-1.min-1.g-1); after recovery, it no longer differed from that in the group B patients (26 +/- 11 versus 22 +/- 4 mm Hg.mL-1.min-1.g-1). MBF during rejection was increased relative to cardiac work, as demonstrated by significantly higher ratios of blood flow to rate-pressure product than those at recovery and in the control patients. CONCLUSIONS: A decrease in hyperemic and an increase in resting myocardial blood flow, in excess to cardiac work, account for the previously reported reduction in coronary flow reserve. Because both alterations improve with antirejection treatment, they may reflect reversible alterations, presumably of endothelial function, local coagulation, and edema. The compromise in flow reserve and hyperemic flows may contribute to acute and chronic injury from rejection and thus provides a rationale for exercise restriction during rejection. The results further suggest a potential role for serial noninvasive flow measurements to guide immunosuppressive therapy.

Adult↗
PubMed1994

Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.

BACKGROUND: Sympathetic excitation characterizes heart failure, but the underlying mechanisms remain unknown. Abnormal baroreflex restraint of sympathetic neural outflow has been proposed, since baroreflexes are known to be abnormal in heart failure. The purpose of this study was to determine if sympathetic activation in humans with heart failure is limited to regions governed by the baroreflexes or is generalized to other regions free from baroreflex control. METHODS AND RESULTS: We report the first direct recordings of skin sympathetic nerve activity (free from baroreflex control) in humans with heart failure and compare simultaneous skin and muscle (baroreflex-dependent) sympathetic peroneal nerve activity in six patients with severe heart failure (mean left ventricular ejection fraction, 0.19 +/- 0.06) and in six age-matched normal control subjects. Although muscle sympathetic nerve activity was markedly increased in heart failure patients (heart failure versus controls, 69 +/- 3 versus 21 +/- 2 bursts per minute; P < .001), skin sympathetic nerve activity was not increased (heart failure versus controls, 12 +/- 1 versus 15 +/- 1 bursts per minute; P = NS). CONCLUSIONS: The finding that skin sympathetic nerve activity in contrast to muscle sympathetic nerve activity is not increased in heart failure supports the concept that an altered reflex system, such as the baroreflexes, with nonuniform effects on muscle and skin sympathetic nerve activity, underlies sympatho-excitation in heart failure.

Adult↗
PubMed1994

Recipient mononuclear cell recognition and adhesion to graft endothelium after human cardiac transplantation. Lymphocyte recognition leads to monocyte adhesion.

Transendothelial migration of mononuclear cells is crucial in the development of allograft rejection and transplant coronary disease. Adhesion of circulating cells to endothelium is the initial step in transendothelial migration. Human aortic endothelial cell cultures were established from aortic tissue harvested at the time of organ donation for cardiac transplantation which allowed specific recipient mononuclear cell-graft endothelial interactions to be studied. Confluent untreated endothelial cells were incubated with recipient mononuclear cells for 15 min to assess adhesion. Adhesion of recipient mononuclear cells to endothelium derived from their graft was threefold higher than adhesion to nonspecific endothelium (93 +/- 20 vs. 30 +/- 11 cells/high power field, P < 0.005). Graft-specific adhesion was inhibited by preincubation of the endothelium with antibodies to class I HLA (34 +/- 16 cells/high power field, P < 0.005). Immunofluorescence performed after adhesion showed that 73 +/- 6% of both specific and nonspecific adherent cells were monocytes. The use of purified lymphocyte and monocyte preparations showed that graft-specific lymphocytes induce unrelated monocytes to become adherent. These results suggest that lymphocytes are primed in vivo to recognize endothelium derived from their graft which leads to a rapid increase in lymphocyte and monocyte adhesion. Such allo-recognition may involve endothelial class I HLA molecules.

CD3 Complex↗
PubMed1993

Impact of left ventricular cavity size on survival in advanced heart failure.

Although left ventricular (LV) dilation has been assumed to be deleterious, the physiologic significance of severe LV dilation in advanced heart failure and its impact on survival have not been defined. LV end-diastolic dimension was measured by M-mode echocardiography in 382 patients with class III or IV heart failure symptoms (mean LV ejection fraction 20 +/- 8%) referred for evaluation for cardiac transplantation. All patients underwent right-sided heart catheterization, and received vasodilator and diuretic therapy adjusted to hemodynamic goals. Although 183 patients with massive LV dilation by LV index > 4 cm/m2 (LV index = LV end-diastolic dimension/estimated body surface area) had a similar severity of hemodynamic impairment to that of 199 patients with only moderate dilation (LV index < or = 4 cm/m2), with baseline mean cardiac index of 2 liters/m/m2 and mean pulmonary arterial wedge pressure of 26 mm Hg in both groups, their actuarial 2-year survival without transplantation was much lower (49 vs 75%; p = 0.004). In the Cox proportional-hazards model, LV index predicted total and sudden death, independent of etiology of heart failure, ejection fraction and other parameters of disease severity. Follow-up echocardiograms (mean 13 +/- 6 months) in 80 heart failure survivors without transplantation showed an increase in mean LV ejection fraction (22 +/- 8% to 26 +/- 13%), but no change in mean LV index in either the massive or moderately dilated groups. Thus, massive LV dilation is an independent contributor to poor outcome in patients with advanced heart failure, and may be stabilized by aggressive vasodilator and diuretic therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Predicting death from progressive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Data were retrospectively reviewed on 528 consecutive patients hospitalized for treatment of advanced heart failure (left ventricular ejection fraction 0.2 +/- 0.07) and cardiac transplant evaluation, who were stabilized with medical therapy and discharged home. Predictors of heart failure death or rehospitalization for urgent transplantation were identified using the Cox proportional-hazards model. Within 1 year, 59 patients (11%) died suddenly and 70 (13%) died of heart failure or required urgent transplantation. A serum sodium < or = 134 mEq/liter, pulmonary arterial diastolic pressure > 19 mm Hg, left ventricular diastolic dimension index > 44 mm/m2, peak oxygen consumption during exercise testing < 11 ml/kg/min and the presence of a permanent pacemaker were independent predictors of hemodynamic deterioration. In the absence of these risk factors the risk of hemodynamic deterioration within 1 year from this study was only 2%. This risk increased to > 50% in the presence of hyponatremia and any 2 additional risk factors. Thus, patients with advanced heart failure at highest risk for progressive hemodynamic deterioration can be identified from clinical variables that could aid in triaging such patients to earlier cardiac transplantation.

Actuarial Analysis↗
PubMed1993

Increased risk of progressive hemodynamic deterioration in advanced heart failure patients requiring permanent pacemakers.

To determine the influence of long-term permanent pacing systems on survival in patients with severe left ventricular dysfunction, data from 557 consecutive patients hospitalized with advanced heart failure for cardiac transplant evaluation and discharged on medical therapy were reviewed. Permanent pacemakers were identified in 42 (8%) patients. One-year actuarial risk of death from heart failure or urgent transplantation in paced patients was higher (49%) than that of a control group, matched for the severity of heart failure (15%, p = 0.003). Sudden death did not differ between paced patients and controls.

Actuarial Analysis↗
PubMed1993

Is intravenous glucocorticoid therapy better than an oral regimen for asymptomatic cardiac rejection? A randomized trial.

OBJECTIVES: This study assessed whether treatment with oral prednisone (bolus plus tapered doses) is comparable to intravenous methylprednisolone sodium succinate (Solu-Medrol) therapy in patients with asymptomatic moderate cardiac allograft rejection episodes without hemodynamic compromise. BACKGROUND: Intravenous Solu-Medrol therapy is frequently administered for moderate rejection episodes after heart transplantation but has not previously been compared with an oral prednisone therapy for asymptomatic cardiac rejection in a randomized trial. Compared with oral prednisone therapy, the administration of intravenous Solu-Medrol is more costly and resource intensive, and it can require loss of work time for patients and the family members who accompany them to treatment. METHODS: Forty-one heart transplant patients with 43 episodes of asymptomatic moderate cardiac rejection were randomized to receive 3 days of 1,000 mg of intravenous Solu-Medrol (20 episodes) or prednisone as a bolus dose of 100 mg orally for 3 days, tapering to the previous maintenance dosage over 14 days (23 episodes). Follow-up endomyocardial biopsies were performed at 2 and 4 weeks. Infectious complications were monitored and the cost of the two forms of therapy was assessed. RESULTS: Resolution of moderate rejection occurred within 4 weeks in 19 (95%) of 20 patients treated with intravenous steroids and in 21 (91%) of 23 patients treated with oral prednisone. No significant difference in infectious complications occurred between the two groups in the ensuing 3 months after therapy. The cost of the oral prednisone therapy was $6.30 compared with the cost of $180 to $966 for administration of intravenous Solu-Medrol. CONCLUSIONS: Oral prednisone (bolus plus tapered doses) appears to be as effective and to have similar infectious complication rates as intravenous Solu-Medrol for the treatment of asymptomatic cardiac rejection. The convenience and lower cost of oral prednisone therapy may warrant its routine use for this type of cardiac rejection.

Administration, Oral↗